Document Detail


Reactive oxygen species generated by NADPH oxidase 2 and 4 are required for chondrogenic differentiation.
MedLine Citation:
PMID:  20952384     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although generation of reactive oxygen species (ROS) by NADPH oxidases (Nox) is thought to be important for signal transduction in nonphagocytic cells, little is known of the role ROS plays in chondrogenesis. We therefore examined the possible contribution of ROS generation to chondrogenesis using both ATDC5 cells and primary chondrocytes derived from mouse embryos. The intracellular level of ROS was increased during the differentiation process, which was then blocked by treatment with the ROS scavenger N-acetylcysteine. Expression of Nox1 and Nox2 was increased upon differentiation of ATDC5 cells and primary mouse chondrocytes, whereas that of Nox4, which was relatively high initially, was decreased gradually during chondrogenesis. In developing limb, Nox1 and Nox2 were highly expressed in prehypertrophic and hypertrophic chondrocytes. However, Nox4 was highly expressed in proliferating chondrocytes and prehypertrophic chondrocytes. Depletion of Nox2 or Nox4 expression by RNA interference blocked both ROS generation and differentiation of ATDC5 cells, whereas depletion of Nox1 had no such effect. We also found that ATDC5 cells depleted of Nox2 or Nox4 underwent apoptosis. Further, inhibition of Akt phosphorylation along with subsequent activation of ERK was observed in the cells. Finally, depletion of Nox2 or Nox4 inhibited the accumulation of proteoglycan in primary chondrocytes. Taken together, our data suggest that ROS generated by Nox2 or Nox4 are essential for survival and differentiation in the early stage of chondrogenesis.
Authors:
Ki Soon Kim; Hae Woong Choi; Hee Eun Yoon; Ick Young Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-01-11     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  40294-302     Citation Subset:  IM    
Affiliation:
Laboratory of Cellular and Molecular Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / pharmacology
Animals
Apoptosis / drug effects
Cell Differentiation / physiology*
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Chondrocytes / cytology,  enzymology*
Chondrogenesis / drug effects,  physiology*
Embryo, Mammalian / cytology,  enzymology*
Enzyme Activation / drug effects
Extracellular Signal-Regulated MAP Kinases / metabolism
Free Radical Scavengers / pharmacology
Hindlimb / embryology,  enzymology
Membrane Glycoproteins / metabolism*
Mice
NADPH Oxidase / metabolism*
Proteoglycans / biosynthesis
Reactive Oxygen Species / metabolism*
Chemical
Reg. No./Substance:
0/Free Radical Scavengers; 0/Membrane Glycoproteins; 0/Proteoglycans; 0/Reactive Oxygen Species; 616-91-1/Acetylcysteine; EC 1.6.-/Nox4 protein, mouse; EC 1.6.3.1/Cybb protein, mouse; EC 1.6.3.1/NADPH Oxidase; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
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